Neuroplasticity and Neuro-Generation: The Promise of Psychedelics in Dementia Care

Abstract

Dementia is a progressive neurodegenerative disease which is characterised by cognitive decline, memory loss, and behavioural changes. Patients suffering from dementia often experience emotional distress, sadness and depression which also impacts the wellbeing of their caregivers. Recent research has explored the potential of psychedelics, such as psilocybin and LSD, when treating various mental health conditions. Psychedelics are known to alter perception, mood and cognition by affecting serotonin receptors in the brain. Studies suggest that psychedelics may be a promising treatment for dementia patients and promote neuroplasticity, reduce neuroinflammation and enhance cognitive flexibility. These effects could potentially lead to a reduction in the progression of neurodegenerative diseases and improve the patients’ quality of life. Additionally, psychedelics might contribute to the prevention of dementia by fostering brain health and resilience against age-related decline. The application of psychedelics in dementia care might pose significant safety and ethical concerns. The present paper provides a narrative review of the existing literature on the use of psychedelics in treatment of dementia and its different types (Alzheimer’s) with the aim to raise awareness on the topic from a critical perspective.

1. Introduction

Dementia represents a growing global health challenge, particularly as populations age and lifespans extend [1]. It is a progressive neurodegenerative disorder characterized by a decline in cognitive functions, including memory, reasoning, language, and the ability to perform everyday activities [2]. The most common forms of dementia include Alzheimer’s disease, vascular dementia, Lewy body dementia, and frontotemporal dementia [3]. The World Health Organisation shares that the prevalence of dementia is increasing at an alarming rate, with millions of new cases diagnosed annually [1]. This rising incidence not only affects the individuals diagnosed but also places an enormous emotional, financial, and logistical burden on families, caregivers, and healthcare systems [4]. The World Health Organization has identified dementia as a public health priority, highlighting the urgent need for more effective treatments and support systems [5].

Despite extensive research into the pathophysiology of dementia, current treatment options remain limited and largely symptomatic [6]. The most widely prescribed medications, such as cholinesterase inhibitors (e.g., donepezil, rivastigmine) and NMDA receptor antagonists (e.g., memantine), provide modest benefits at best and do not alter the underlying progression of the disease [7]. As discussed by the World Dementia Council non-pharmacological interventions, including cognitive stimulation and behavioural therapies, can offer some symptomatic relief, but these are not universally effective and often require intensive resources. As a result, the search for novel therapeutic approaches has intensified, particularly those that can target the disease at a biological level while also addressing the emotional and psychological distress commonly experienced by patients and their caregivers.

In recent years, there has been a resurgence of interest in the therapeutic potential of psychedelics, such as psilocybin (the active compound in “magic mushrooms”) and lysergic acid diethylamide (LSD) [8]. Once dismissed and stigmatized due to their association with countercultural movements and legal restrictions, these substances are now being revisited through a scientific lens. A growing body of research suggests that psychedelics may have profound effects on mood, cognition, and brain plasticity [9]. Their mechanisms of action, particularly through the serotonin 5-HT2A receptor, position them as promising candidates for a range of psychiatric and neurological disorders, including depression, anxiety, PTSD, and possibly dementia [10].

This review aims to examine the potential role of psychedelics in the treatment of dementia. It will explore the biological underpinnings of dementia and the mechanisms through which psychedelics may exert neuroprotective and cognitive-enhancing effects. The review will also consider the psychological benefits these substances may offer, particularly in alleviating emotional distress associated with dementia. Furthermore, it will address the ethical, legal, and safety considerations surrounding the use of psychedelics in vulnerable populations. By synthesizing current evidence and identifying key gaps in knowledge, this paper seeks to provide a comprehensive overview of an emerging and potentially transformative area of research.

2. Dementia: Pathophysiology and Current Treatments

Dementia encompasses a spectrum of neurodegenerative diseases that are characterized by progressive deterioration in cognitive function, emotional regulation, and behaviour [11]. Although Alzheimer’s disease (AD) is the most prevalent and widely studied form, other subtypes such as vascular dementia, Lewy body dementia (LBD), and frontotemporal dementia (FTD) also contribute significantly to the overall burden of disease [12]. Dening explains that each subtype is associated with distinct pathological features, although overlapping mechanisms are often observed. Understanding these differences is crucial for developing targeted interventions.

Wenk [13] explains that Alzheimer’s disease is primarily associated with the accumulation of amyloid-beta plaques and neurofibrillary tangles composed of hyperphosphorylated tau protein. These pathological changes lead to synaptic dysfunction, neuronal loss, and ultimately, widespread brain atrophy. In addition to these hallmark features, neuroinflammation and oxidative stress have emerged as key contributors to disease progression [14]. Vascular dementia, on the other hand, is typically caused by reduced blood flow to the brain, often as a result of stroke or chronic small vessel disease [15]. The resulting ischemic damage impairs neuronal function and connectivity. Lewy body dementia is characterized by the presence of alpha-synuclein aggregates, known as Lewy bodies, which disrupt neuronal signalling and contribute to both cognitive and motor symptoms [16]. Frontotemporal dementia involves the progressive degeneration of the frontal and temporal lobes, with associated changes in behaviour, personality, and language [17].

Table 1. Pathology, symptoms and treatments for different types of dementia (adapted from [18,19]).

	Alzheimer’s Disease (AD)	Vascular Dementia (VaD)	Lewy Body Dementia (LBD)	Frontotemporal Dementia (FTD)
Pathology	Amyloid-beta plaques—Neurofibrillary tangles (tau)—Neuroinflammation, oxidative stress	Ischemic damage due to reduced cerebral blood flow—Often follows stroke or chronic small vessel disease	Alpha-synuclein aggregates (Lewy bodies)—Disruption of neurotransmission	Neuronal loss in frontal and temporal lobes—Tau or TDP-43 protein inclusions
Symptoms	Memory loss (esp. short-term)—Disorientation—Language difficulties—Apathy, mood swings	Impaired executive function—Slowed thinking—Gait disturbance—Mood changes—Often stepwise progression	Visual hallucinations—Parkinsonism (rigidity, tremor)—Fluctuating cognition—REM sleep behaviour disorder	Personality changes—Apathy, disinhibition—Language deficits (aphasia)—Poor judgment
Affected Brain Regions	Hippocampus—Entorhinal cortex—Parietal and temporal lobes	Subcortical white matter—Frontal lobes (executive dysfunction)—Areas affected by infarcts	Basal ganglia—Brainstem—Occipital lobes (visual processing)—Frontal cortex	Frontal lobes (behavioural variant)—Temporal lobes (semantic/language variant)
Onset & Progression	Gradual, progressive	Often sudden or stepwise—May progress in stages	Fluctuating course—Can mimic AD or Parkinson’s	Early onset (often <65) Gradual, progressive
Current Treatments	Cholinesterase inhibitors (donepezil, rivastigmine)—NMDA antagonist (memantine)—Aducanumab (controversial)—Lifestyle modification	Treat underlying vascular risk (hypertension, diabetes)—Antiplatelet therapy—Cognitive rehab	Cholinesterase inhibitors (some benefit)—Levodopa (for motor symptoms, limited)—Avoid antipsychotics	Symptomatic only—SSRIs (for behavioural symptoms)—Speech and occupational therapy

provides an overview of the pathology, symptoms, and treatments for different types of dementia.

Despite the heterogeneity of dementia types, current treatment strategies are largely uniform and focus on symptomatic management [20]. As Buckley and Salpeter [21] discuss, Cholinesterase inhibitors such as donepezil, galantamine, and rivastigmine aim to enhance cholinergic transmission in the brain, which is often compromised in dementia patients. Memantine, an NMDA receptor antagonist, is used to modulate glutamatergic signalling and protect against excitotoxicity. While these medications can provide temporary improvements in cognition and behaviour, their efficacy diminishes over time, and they do not halt or reverse neurodegeneration.

Non-pharmacological interventions, including cognitive rehabilitation, occupational therapy, and lifestyle modifications, can also play a role in managing symptoms and maintaining functional abilities [22]. These approaches often require a multidisciplinary team and are most effective when tailored to individual patient needs. However, access to such services is often limited by resource constraints and geographical disparities. In light of these challenges, there is a pressing need for novel therapies that not only alleviate symptoms but also modify disease progression [23]. Increasingly, researchers are turning to unconventional avenues, including the use of psychedelics, to explore new possibilities for dementia care [24].

3. Psychedelics: Mechanisms of Action

Psychedelics are a class of psychoactive substances that produce profound alterations in perception, mood, and cognition [25]. Among the most studied are psilocybin and LSD, both of which exert their effects primarily through agonism of the serotonin 5-HT2A receptor [26]. Cameron explains this receptor is abundantly expressed in the prefrontal cortex and other brain regions involved in higher-order cognitive functions, emotional regulation, and consciousness. Activation of 5-HT2A receptors leads to a cascade of intracellular events that enhance neuronal excitability and modulate synaptic transmission [27].

One of the most intriguing aspects of psychedelic action is their ability to promote neuroplasticity [28]. Preclinical studies have demonstrated that psychedelics can stimulate the growth of dendritic spines, increase synaptogenesis, and enhance the expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) [29]. These effects suggest a potential for reversing or compensating for the synaptic loss and network disruptions observed in neurodegenerative diseases like dementia [30]. Furthermore, as Gattuso [31] explains, psychedelics have been shown to modulate the default mode network (DMN), a set of interconnected brain regions that are active during rest and self-referential thought. In conditions such as depression and Alzheimer’s disease, the DMN often exhibits hyperconnectivity and rigidity [32]. Psychedelics appear to disrupt this pattern, allowing for greater network flexibility and integration, which may underlie some of their therapeutic benefits [33]. Figure 1 [34] illustrates the serotonin receptor pathways affected by psychedelics and the resulting changes in connectivity and neuroplasticity.

In addition to their neurobiological effects, psychedelics can induce powerful psychological experiences that may have therapeutic value [35]. Users often report a sense of ego dissolution, heightened emotional awareness, and profound insights during psychedelic sessions [36]. These experiences are thought to facilitate emotional processing and psychological healing, particularly in individuals suffering from depression, anxiety, or trauma [37]. In the context of dementia, where patients often experience significant emotional distress and a loss of identity, the ability of psychedelics to promote emotional breakthroughs and a sense of connection may offer meaningful relief [38].

Moreover, psychedelics have been found to exert anti-inflammatory effects in the brain, which could be particularly relevant for neurodegenerative conditions characterized by chronic neuroinflammation [39]. Nichols [40] explains that by modulating immune responses and reducing the production of pro-inflammatory cytokines, psychedelics may help create a more favorable environment for neuronal survival and repair. While much of this evidence comes from animal models and small-scale human studies, it lays the groundwork for further investigation into the potential role of psychedelics in treating and possibly preventing dementia [41].

As research progresses, it is becoming increasingly clear that psychedelics represent a multifaceted intervention with both biological and psychological dimensions. Their unique ability to simultaneously influence brain structure, function, and subjective experience positions them as promising candidates for addressing the complex and multidimensional nature of dementia [42]. However, rigorous clinical trials and careful ethical considerations will be essential to determine their safety, efficacy, and appropriate use in this vulnerable population.

4. Psychedelics in Mental Health Research

Over the past two decades, there has been a resurgence of interest in the therapeutic potential of psychedelic substances, particularly in the context of treating mental health disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD). Substances such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), and 3,4-methylenedioxymethamphetamine (MDMA) have been revisited in clinical settings after decades of legal and cultural prohibition. Controlled clinical trials have demonstrated promising outcomes, particularly for patients with treatment-resistant forms of depression and anxiety [43]. For example, psilocybin has shown rapid and sustained antidepressant effects in randomized controlled trials involving participants with major depressive disorder and cancer-related psychological distress [44]. These effects are often observed after one or two dosing sessions, suggesting a mechanism of action that is distinct from traditional antidepressants such as SSRIs or SNRIs [45].

In patients with PTSD, MDMA-assisted therapy has garnered particular attention, with Phase 3 clinical trials reporting significant reductions in PTSD symptoms [46]. These reductions are often sustained months after treatment and have been associated with improved emotional processing and trauma integration, Krediet explains. These outcomes have been attributed to the ability of psychedelics to facilitate profound psychological experiences, often involving increased emotional openness, reduced fear response, and enhanced memory reconsolidation, that can be therapeutically transformative when combined with guided psychotherapy [47].

The relevance of these findings to dementia care lies in the significant overlap between the psychiatric symptoms treated in these trials and those commonly experienced by dementia patients. Depression, anxiety, existential distress, and feelings of isolation are pervasive among individuals diagnosed with dementia and their caregivers [48]. These symptoms not only reduce quality of life but may also exacerbate cognitive decline and neurodegenerative processes through mechanisms like chronic stress, inflammation, and social withdrawal [49]. Psychedelics’ ability to elicit meaningful emotional breakthroughs, enhance mood, and promote a sense of connectedness offers a unique therapeutic pathway that differs markedly from traditional pharmacologic interventions, which often target symptoms in isolation without addressing the broader psychosocial context [24].

A critical factor in psychedelic therapy is the concept of set and setting, which refers to the individual’s mindset (set) and the physical and social environment (setting) in which the psychedelic experience takes place [50]. These variables are essential to therapeutic outcomes and underscore the need for professional supervision and structured integration practices. The importance of the therapeutic alliance, preparation before dosing, and integration afterward cannot be overstated, particularly when considering vulnerable populations such as the elderly or cognitively impaired [51].

Safety and dosage are other crucial considerations in psychedelic-assisted therapy. While the classic serotonergic psychedelics (e.g., psilocybin, LSD) have low physiological toxicity and do not appear to induce dependence, psychological risks such as transient anxiety, confusion, or perceptual disturbances can occur, particularly in unsupervised or poorly structured contexts [52]. In clinical trials, adverse events are rare and typically self-limited, but special caution is warranted when considering their use in patients with comorbidities or neurodegenerative diseases [53]. Dosage must be carefully calibrated, often beginning with a low to moderate dose under expert supervision, followed by rigorous post-session evaluation [54].

In addition to the use of serotonergic psychedelics, esketamine, a stereoisomer of ketamine, has gained regulatory approval for treatment-resistant depression and is distinguished by its rapid onset of antidepressant effects and neuroplastic mechanisms. Acting primarily as an NMDA receptor antagonist, esketamine enhances glutamatergic transmission and downstream synaptogenesis, contributing to its therapeutic efficacy. Related compounds such as arketamine, rapastinel, and zuranolone similarly target glutamatergic or GABAergic pathways and are under clinical development or use, reflecting a paradigm shift toward fast-acting agents that promote adaptive neural remodeling in mood disorders.

Given the growing body of literature supporting the use of psychedelics in treating emotional and psychological disorders, there is an emerging interest in exploring their application in populations affected by neurodegeneration. However, such an extension must be approached with caution and guided by robust clinical evidence, ethical oversight, and personalized care models.

5. Evidence for Psychedelics in Dementia Care

Although most contemporary psychedelic research has focused on younger or middle-aged adults with psychiatric conditions [28], there is a growing body of preclinical and theoretical literature suggesting that psychedelics may also be relevant for individuals with neurodegenerative diseases such as dementia [30]. Preclinical studies in animal models have shown that psychedelics may promote neurogenesis and synaptic plasticity, especially in the hippocampus—a region critical to memory and learning that is significantly affected in Alzheimer’s disease [55]. Substances like psilocybin and DMT have demonstrated the capacity to upregulate brain-derived neurotrophic factor (BDNF) [56], a protein involved in the survival and growth of neurons, which is often depleted in neurodegenerative conditions [57].

In rodent models, microdoses of psychedelics have been associated with increased dendritic spine density and improved performance in tasks measuring cognitive flexibility and memory retention [58]. Moreover, these compounds may exert anti-inflammatory effects by modulating immune signaling pathways and reducing pro-inflammatory cytokine levels [41]. Given that neuroinflammation is a key driver in many types of dementia, these findings suggest that psychedelics could play a neuroprotective or disease-modifying role, not merely a palliative one [59].

Clinical evidence, although still limited, is beginning to emerge. Anecdotal reports, small-scale observational studies, and pilot trials have suggested that psychedelics may improve mood, reduce anxiety, and enhance well-being in older adults [60]. For example, there have been documented cases of elderly individuals undergoing psilocybin-assisted therapy reporting a renewed sense of purpose, reduced fear of death, and improved interpersonal relationships, factors that can significantly impact dementia trajectories [61]. Some trials have included older patients with early cognitive decline or mild cognitive impairment (MCI), and preliminary results indicate that, when carefully monitored, psychedelic interventions are not only tolerated but may offer measurable psychological benefits [62].

These early indications are now being put to rigorous scientific scrutiny. At the Center for Psychedelic and Consciousness Research at Johns Hopkins University, Drs. Albert Garcia-Romeu and Paul B. Rosenberg are conducting pioneering work examining the use of psilocybin in patients with Alzheimer’s disease and related dementias (ADRDs) [63,64]. Their research builds on two decades of work with psilocybin in populations facing major depression, terminal illness, and addiction. In these earlier studies, participants reported profound reductions in anxiety and depression, with more than 80% of cancer patients citing increased life satisfaction and a renewed sense of purpose following treatment [65]. These outcomes have laid a promising foundation for applying psychedelic-assisted therapy to dementia populations, especially given the high prevalence of psychiatric comorbidities such as anxiety and depression, affecting nearly 40% of people with Alzheimer’s disease [66]. Even though, there is hope that psychedelics might become an effective alternative treatment to dementia, it is crucial to acknowledge that data on their effectiveness is currently limited and anecdotal. As such, this limited evidence base amongst dementia patients should not be overlooked.

Importantly, traditional interventions for mood disturbances in dementia, such as SSRIs and cognitive behavioral therapy, have limited efficacy. SSRIs often take weeks to act, may not be well tolerated in older adults, and frequently fail to improve core symptoms of anxiety in dementia populations [67]. Psychedelics, by contrast, can induce rapid, durable changes in mood and cognition after a single guided session [68]. It is explained that psilocybin, in particular, works by stimulating serotonin 5-HT2A receptors in the brain, leading to increased connectivity across brain regions, reduced activity in the default mode network (DMN), and enhanced emotional processing. These effects contribute not only to acute mood relief but also to shifts in perception and meaning-making that can alleviate existential distress [69].

6. Ethical, Legal, and Safety Considerations

While the therapeutic potential of psychedelics in dementia care is increasingly recognized, their use raises significant ethical, legal, and safety concerns that must be addressed with rigor and sensitivity [42]. One of the foremost considerations is the vulnerability of the target population. Elderly individuals, particularly those with cognitive impairments, may be more susceptible to adverse effects due to age-related changes in metabolism, cardiovascular health, and neural plasticity [70]. Ensuring that psychedelic interventions are safe and appropriately tailored for such individuals is a complex task that requires careful screening, dosing, and monitoring protocols [71].

McManus [72] explains that psychological risks must also be considered. While adverse events in clinical settings are rare, psychedelics can induce transient episodes of anxiety, confusion, or hallucinations. These effects may be particularly disorienting for individuals with dementia, who may already experience perceptual or memory disturbances. As such, strict inclusion criteria should be implemented, and only those in the early stages of cognitive decline may be suitable candidates. Comprehensive medical evaluations and ongoing supervision by trained clinicians are essential components of a safe therapeutic framework.

Informed consent presents a further ethical challenge [73]. Many individuals with moderate to advanced dementia may lack the capacity to fully understand the risks and implications of psychedelic therapy, Marks highlights. Legal guardianship, advance directives, and careful ethical review processes must be in place to ensure that vulnerable patients are not exposed to interventions they cannot adequately evaluate or decline.

Legally, psychedelics remain classified as Schedule I substances in many jurisdictions, meaning they are considered to have high abuse potential and no accepted medical use [74]. While regulatory attitudes are slowly shifting, significant legal barriers remain. Research is often confined to highly controlled academic environments, and clinical access is limited. Policymakers and ethics boards will need to develop new guidelines as the evidence base grows and public interest increases.

Phelps [75] discusses that there is also the broader risk of misuse or commercialization without sufficient oversight. As interest in psychedelics grows, so too does the potential for unregulated, non-clinical use, particularly among vulnerable populations. Ensuring that psychedelic interventions are delivered within ethical, evidence-based frameworks will be essential to avoid harm and safeguard public trust.